It is known that intestinal epithelial cells (IECs) interact with immune cells to modulate intestinal or systemic immune responses. Dendritic cells (DCs) are one crucial component in maintaining intestinal immune tolerance. However, how IECs and DCs collaborate to maintain the gut immune balance is still unclear. We further found that one transcription factor Foxo1, plays a critical role for IECs function. The loss of Foxo1 within IECs leads to altered mucus layer formation and DCs function. Consequently, mice without Foxo1 in IECs exhibit enhanced susceptibility to intestinal inflammation. We have hypothesized that IEC-derived Foxo1 regulates the IEC-DC interaction for intestinal tolerance via mucin protein. We are currently studying the cellular and molecular mechanisms of how Foxo1 regulates IECs interaction with DCs.